title: The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.
abstract: BACKGROUND
  Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation.
  
  
  OBJECTIVE
  We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon.
  
  
  METHODS
  We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively.
  
  
  RESULTS
  Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001).
  
  
  CONCLUSIONS
  MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom (J Hanks, IA, NK, AG, CLL, PE, and MP), and the Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom (CR, J Harris, and MP).
authors.forename: Joanna
authors.initials: J
authors.lastname: Hanks
authors.forename: Iyeman
authors.initials: I
authors.lastname: Ayed
authors.forename: Neil
authors.initials: N
authors.lastname: Kukreja
authors.forename: Chris
authors.initials: C
authors.lastname: Rogers
authors.forename: Jessica
authors.initials: J
authors.lastname: Harris
authors.forename: Alina
authors.initials: A
authors.lastname: Gheorghiu
authors.forename: Chee Ling
authors.initials: CL
authors.lastname: Liu
authors.forename: Peter
authors.initials: P
authors.lastname: Emery
authors.forename: Maria
authors.initials: M
authors.lastname: Pufulete
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004032:Diet / Q000009:adverse effects; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D056726:Genetic Association Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)